[Mechanisms of secondary degeneration in the central nervous system during acute neural disorders and white matter damage]. / Mecanismos de degeneración secundaria en el sistema nervioso central durante los trastornos neuronales agudos y el daño en la sustancia blanca.

INTRODUCTION: Acute neurodegenerative diseases, including stroke and traumatic brain and spinal cord injury, possess an elevated worldwide incidence. Two distinct lesive patterns can be identified after these destructive events: primary damage, an early consequence of the primary pathological event, and secondary neural degeneration (SND), a group of pathological events inducing late degeneration in cells not or even only partially affected by the primary damage. This pathological mechanism is an important contributing factor for functional deficits and target for therapeutic approaches. Several factors are involved on the SND etiology, including excitotoxicity, inflammation, and oxidative stress. AIM: To review the main mechanisms underlying the SND occurring after acute neural disorders. DEVELOPMENT: The more recent findings about the eliciting processes of SND degeneration are discussed, as well as their significance to degeneration of white matter tracts. CONCLUSIONS: The characterization of the events underlying SND is of fundamental importance for the development of new therapeutic approaches effective enough to decrease the functional deficits, contributing to the improvement of the quality of life of people suffering neurological diseases. These therapeutic approaches must be validated in experimental models of both brain and spinal cord diseases, which effectively simulate human neural disorders protecting both gray and white matters for a better neuroprotective efficacy.

Inflammatory response and white matter damage after microinjections of endothelin-1 into the rat striatum.

Following acute and chronic neurodegenerative disorders, a cascade of pathological events including inflammatory response, excitotoxicity and oxidative stress induces secondary tissue loss in both gray and white matter. Axonal damage and demyelination are important components of the white matter demise during these diseases. In spite of this, a few studies have addressed the patterns of inflammatory response, axonal damage and demyelination following focal ischemic damage to the central nervous system (CNS). In the present study, we describe the patterns of inflammatory response, axonal damage and myelin impairment following microinjections of 10 pmol of endothelin-1 into the rat striatum. Animals were perfused at 1 day, 3 days and 7 days after injection. 20 mum sections were stained by hematoxylin and immunolabeled for neutrophils (anti-MBS-1), activated macrophages/microglia (anti-ED1), damaged axons (anti-betaAPP) and myelin (anti-MBP). The evolution of acute inflammation was quantitatively assessed by cell counts in different survival times. There was recruitment of both neutrophils and macrophages to the damaged striatal parenchyma with maximum recruitment at 1 day and 7 days, respectively. Progressive myelin impairment in the striatal white matter tracts has been observed mainly at later survival times. beta-APP+ endbulbs were not present in all evaluated time points. These results suggest that progress myelin impairment in the absence of damage to axonal cylinder is a feature of white matter pathology following endothelin-1-induced focal striatal ischemia.